PROJECT SUMMARY Methods that improve upon the temporal resolution of current fMRI techniques are urgently needed to better understand the temporal characteristics of healthy brain function and to better identify the drivers of brain dysfunction. Our current functional Magnetic Resonance Elastography (fMRE) data shows that functionally activated regions of the brain undergo a change in their mechanical stiffness. These mechanical changes are observed at frequencies as high as 10Hz, which is two orders of magnitude faster than traditional fMRI. The mechanism is therefore either directly related to, or closely coupled to, primary neuronal activity. Prior work has primarily been in anesthetized mice with electrical stimulation of the hind limb as the functional stimulus. In this proposal, the aims are to establish fMRE as a viable methodology to measure brain function in humans and to test its ability to follow the propagation of neuronal activity at high temporal resolution. The first part of this proposal will be to implement several hardware and software modifications to improve data quality. Then, in a cohort of 10 healthy adult subjects, the reproducibility of fMRE in humans will first be studied by comparing the elasticity response between two stimulus states. Differences in the elasticity response that depend on the length of time of the stimulus state, either 840ms or 37 seconds, will be examined. At the longer ?residence time? of 37 seconds, one expects to see the effects of the slow neurovascular coupling while only the primary neuronal response is expected for 840ms. As a further check of the ability of fMRE to measure function, a hemi- field stimulus will be applied where a contralateral brain function response is expected. A final goal is to demonstrate the power and scope of fMRE to follow the temporal propagation of dynamic neuronal activity. This will be done using a five-segment stimulus protocol where the stimulus is ON-OFF-OFF-OFF-OFF. Five different elasticity maps will then be obtained that will allow one to follow the elasticity response as a function of time. The temporal resolution, i.e. the length of time for each stimulus state (ON or OFF) will be varied between 24 and 120ms. The perceptual response in the visual cortex pathway areas will be measured with different retinotopic mapping stimuli. The discovery of functionally dependent changes in in vivo brain tissue stiffness opens a novel methodology to achieve functional brain mapping at both high spatial and temporal resolution. It has great potential to facilitate and deepen our understanding of the pathway of neuronal signals propagating in the in vivo brain, including the elucidation of impaired neural circuitry associated with pathologic sub-components of neuronal physiology.